The ultimate goal of this research project is to develop concepts which may be useful toward inducing therapeutically favorable imbalances of antitumor host defenses through the effects of certain anticancer drugs. The identification and clarification of the mechanisms of immunomodulation by adriamycin, new anthracyclin analogs with improved and novel therapeutic potential, and 6-mercaptopurine are among the immediate goals. The therapeutic potential of inhibiting suppressor functions as a means to augment antitumor host responses will be explored. The possible differences between restoration and augmentation of antitumor cellular immunity by adriamycin will be studied. The usefulness of syngeneic versus allogeneic tumor-host systems and that of in vivo versus in vitro systems for studies of immunomodulation by anticancer drugs will be evaluated. In these investigations, spleen cells from drug treated and/or immunized mice will be separated using adherence and specific cell markers methodologies; these separations would be required to identify the specific targets of drug action responsible for the drug-induced immunomodulation. Host defenses will be measured according to effects on various functions including phagocytosis, cytolysis of target cells, tumor growth inhibition, suppression of response. The research proposed herein is related to the possibility of deliberately using anticancer drugs not only an antiproliferative but also as immunomodulating agents. It is now a reasonable assumption that cancer chemotherapy may have therapeutic cooperative interactions with residual or immunotherapeutically augmented defenses of the host. Not yet clear, however, is the possibility that some of the clinically used anticancer agents may exert immunomodulating effects which may be therapeutically exploitable in cooperation with their own antitumor effects or that of other therapies. It is towards the clarification of this possibility that the program of the P.I. has been directed in recent years, using a few drugs as probes. This approach is different from that pursued by other laboratories concerned with immunotherapy and has provided a measure of uniqueness to this program.